Abnormal Cell Responses and Cancer Progression

Mary Beckerle, PhD serves as the CEO and Director of the Huntsman Cancer Institute, her current research focuses on understanding the fundamental mechanisms by which cells sense and respond to environmental signals. Her scientific contributions have been acknowledged by the National Cancer Institute, and she was the proud recipient of the latest Alfred G. Knudson Award in Cancer Genetics. The beauty of biological systems and the creativity involved in designing scientific experiments were key to establishing Mary’s interest in science.

Q: What particularly inspired you to pursue a career in science? 

A: I chose a career in science because science represented a discipline where I could do something I loved and could also have the potential for meaningful impact on society. I always loved biology as a young student. I was captivated by the beauty of biological systems and the creativity involved in designing experiments to answer questions about how the living world works. I remember biology lab in high school as being one of my favorite classes. At the same time, I was a child of the 1960’s and was only interested in doing something meaningful where I could make a difference in society. Science also provided that opportunity which, for me, was at the interface of science and medicine. Happily, I had both an appetite and an aptitude for biology. As a result, I was encouraged by great teachers and mentors and had wonderful opportunities to explore and develop my skills. I spent three summers at The Jackson Labs and completed an internship in a laboratory at Memorial Sloan-Kettering Cancer Center while in college. These experiences solidified my love for science and medicine.  

Q: Could you tell us more about your current research interests and area of expertise?

A: I am a cell biologist. Cells are the fundamental unit of life and the differentiated functions of cells underlie all of human physiology. Cells in the human body receive many types of signals that influence their function. For example, growth factors stimulate cells to divide if an organ needs to grow or be repaired. My lab is focused on understanding the fundamental mechanisms by which cells sense and respond to environmental signals. In recent years, we have focused on a new frontier in this area, the mechanism by which cells respond to mechanical cues. It is now recognized that mechanical signals exert significant influences on cells, but we are only now beginning to understand how physical forces are sensed by cells and how they impact cell behavior. So, it is a very exciting time to be working in this field. 

Q: You recently won the Alfred G. Knudson Award in Cancer Genetics from the National Cancer Institute (NCI). How did it feel to win the award?

A: I was completely surprised and incredibly honored to be recognized by the National Cancer Institute (NCI) with this distinction — particularly when I saw the list of prior recipients of the award, which includes some of the most talented and creative scientists in the world today.

As I had a chance to reflect on the meaning of this recognition, I also very much appreciated that the NCI was celebrating contributions like those from my lab which are focused on fundamental aspects of cell biology. Those of us in the cancer research community appreciate that the exciting advances that have been made in cancer medicine — including new strategies for prevention and treatment of cancers — have been made possible in large part because of our national investment in basic science discovery. We have been making great progress in applying our deepening knowledge of fundamental biological principles to clinical cancer challenges.  This has led to a significant reduction in cancer mortality that clearly manifested as an increase in cancer survivors in the United States from just 3 million in 1971 when the “War on Cancer” was initiated, to more than 15 million today. I am excited that the NCI continues to demonstrate that it values basic science contributions as critical to our national cancer strategy.

Q: Could you tell us more about your award lecture “Interface Between Cytoskeletal Dynamics and Tumor Biology”?

A: In my award lecture, I discussed my lab’s effort to understand how cells respond to mechanical signals in their environment. We now appreciate that mechanical signals can stimulate changes in cell growth and cell death. And we know that tumor cells display abnormal responses to mechanical cues, which contribute to cancer initiation and progression. My lab has developed a technology that allows us to physically stretch cells using defined parameters, so we can study the response of cells to physical force under controlled experimental conditions. Using this technology coupled to biochemical analyses and high-resolution cell imaging approaches, we have identified a novel pathway by which mechanical forces are sensed at the cell surface and communicated all the way to the nucleus of the cells, where changes in gene expression can drive fundamental changes in cell behavior, such as cell proliferation or death. This pathway involves the reinforcement of the actin cytoskeleton, a major structural and contractile element of cells. I also described how the ability of cells to respond to mechanical stress is disrupted in tumor cells. 

Q: Are there any research areas you are yet to explore that you would be eager to investigate in the future?

A: We continue to dive deeper in order to understand the response of cells to mechanical stress at a detailed mechanistic level. At the same time, we are interested in the application of this knowledge in the context of cancer biology. Working with a number of oncology colleagues at Huntsman Cancer Institute, we have been exploring how some of the processes we have discovered are disturbed in tumors, such as Ewing sarcoma, a childhood bone cancer. We are excited that one of our collaborators, Dr Sunil Sharma, has developed a new small molecule agent that reverses the changes that occur during Ewing sarcoma development. We are excited that we have been able to contribute to understanding the impact of this promising new therapeutic approach for Ewing sarcoma cell biology. We expect clinical trials of this new therapeutic approach to be initiated this year; we are hopeful that the promising preclinical findings of our collaborative team will be replicated in patients, bringing a new treatment to patients with a now incurable cancer. 

Q: What can be done to encourage more women to get involved in science?

A: I think that one of the most important factors that influences career choice is the availability of role models. In my own case, even though there were very few women in science when I decided to go to graduate school, I had the benefit of having a wonderful female faculty advisor when I was in college. Thus, I could envision myself as a scientist and a faculty member.

Although things have improved since I was in graduate school in the 1980’s, still only about 20% of full professors in science fields are women. This situation perpetuates the view that science and engineering are fields for men. If our nation is going to capitalize on our talent, half of which resides in the female half of our population, we must have a welcoming professional environment for young women interested in science. That means being attentive to expanding gender diversity within our university faculties and other scientific career roles. (Similar arguments apply to racial and ethnic diversity as well.) In addition, we need to ensure that career paths for women in science are attractive and don’t force women to have to make a choice between career and family. For women who are considering a scientific career in academia, for example, the tenure clock is often on a collision course with the biological clock. Institutions that will be successful in recruiting and retaining top female scientific talent will be places where women are supported in their professional, as well as their personal, aspirations. For example, universities that support extension of tenure decision timelines for parenting or other family obligations, will send a message to faculty (both women and men) that the institution values and supports them both as a person and as a scientist. 

Mary Beckerle, PhD was speaking to Laura Elizabeth Mason, Science Writer for Technology Networks.